Interview | Winners of the 2014 Algerian Paper of the Year Award in Medicine, Pharmacy & Veterinary Sciences

ByRomaissa Asme Boussahel

Interview | Winners of the 2014 Algerian Paper of the Year Award in Medicine, Pharmacy & Veterinary Sciences

Mr Jamal Tahtat is a researcher at the Department of Irradiation Therapy in the Nuclear Research Center of Algiers. He is the first author of the paper that won the 2014 Algerian Paper of the Year Award in Medicine, Pharmacy and Veterinary Sciences entitled “Oral delivery of insulin from alginate/chitosan crosslinked by glutaraldehyde” and which published in the International Journal of Biological Macromolecules. Inspire magazine speaks to Mr Tahtat about the work reported in the award winning paper.

Inspire Magazine: Thank you for speaking to Inspire Magazine, and many congratulations for winning the 2014 Algerian Paper of the Year Award in Medicine, Pharmacy and Veterinary Sciences. How do you feel about winning this award?

TahtatMr. Tahtat: Thank you very much for the congratulations and also for the great initiative to create the Algerian Network for Academics, Scientists and Researchers. I am very pleased and feel very proud to win the 2014 Algerian Paper of the Year Award in Medicine, Pharmacy and Veterinary Sciences. I would like to take this opportunity to thank the institute of Nuclear Research Center of Algiers for their facilities, which enabled this research to take place. I would also like to thank my co-authors Mr. Mahlous, Mrs. Benamer, Mrs. Nacer khodja, Mrs. Oussedik and Mrs. Laraba. I dedicate this prestigious award to my family and all my colleagues from Nuclear Research Center of Algiers and all my former professors for their informed guidance.

IM: In simple terms, can you tell us what the winning paper is about?

Mr. Tahtat: The aim of the study reported in the paper is to formulate a novel drug delivery system from alginate beads that would enable the oral delivery of insulin. Which is a much more convenient form of delivery when compared to subcutaneous ways, as it is less invasive. We achieved this through the reinforcement of calcium alginate matrices with chitosan and then crosslinking them by glutaraldehyde. This resulted in matrices with improved mechanical properties that could withstand the stresses of the simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The matrices also prolong the release profile of insulin in intestinal media.

IM: Why is it difficult to deliver insulin?

Mr. Tahtat: Insulin is the most effective drug used to control blood glucose levels. However, in clinical therapy, insulin is mainly administered via subcutaneous route. This tends to cause pain and discomfort and possible infections, thus, leading to a lower patient compliance, with some diabetic patients neglecting and even giving up entirely on Insulin therapy. For this reason, alternative routes of insulin administration are very promising and have been the center of investigation. However, several problems are encountered for the development of oral insulin delivery system, the most important of which is the degradation of insulin by proteolytic enzymes and the acidic environment in the stomach and the low penetration of insulin across the lining of the intestine into the blood stream. One promising strategy to improve the oral bioavailability and gastrointestinal uptake of insulin is to load it into natural and polymeric carriers as delivery vehicles.

IM: Your award winning paper describes a method to load Insulin into Alginate/Chitosan beads. What is the rationale behind the decision to use these particular polymers to carry insulin?

Mr. Tahtat: Alginate and Chitosan are natural polymers; they fall into a class of molecules known as polysaccharides. This class of molecules encompasses all naturally occurring sugars. As such they are biodegradable, biocompatible and non-toxic and are very promising for clinical applications. The main disadvantage of such molecules is their soft structure and poor mechanical properties, which we overcome with the strategies proposed in the paper.

Alginate is most abundant polysaccharide in nature and distributed widely in the cell walls of brown algae. It contains two uronic acids, mannuronic acid (M) and guluronic acid (G). In addition, sodium alginate has a unique property of crosslinking in the presence of multivalent cations to form the egg box junctions. Alginate is pH sensitive; it remains stable in the acidic pH of stomach, and swells and dissolves in the intestinal alkaline pH. Alginate has been considered one of the most suitable biopolymers for encapsulation material allowing the entrapment of a wide range of substances.

Similarly, Chitosan is a polysaccharide composed of repeating units of acetyl-D-glucosamine. It is derived from chitin, a major component of the crustacean exoskeletons. It is a non-toxic, biocompatible cationic polysaccharide produced by partial deacetylation of chitin. Chitosan is well known for its mucoadhesive properties, which may allow a prolonged interaction of the delivered drug with the epithelia membrane, facilitating more efficient absorption.

IM: How do you produce these beads? And what is the mechanism by which the beads deliver Insulin into the small intestines and across the gastrointestinal mucosa?

Mr. Tahtat: A gelation process produces the beads using a droplet method. To ensure good mixing and for ideal blend with sodium alginate, the molecular weight of the chitosan was depolymerized by radiolysis using gamma radiation of Co60. The blend solution containing sodium alginate and chitosan was prepared with different mass proportions. A given amount of sodium alginate was dissolved in distilled water under mechanical stirring. The chitosan powder was added into the solution and mixed homogeneously. Chitosan was dissolved by adding acetic acid into the mixture. A homogeneous blend solution of the two biopolymers was formed under stirring. The blend solution was then dripped through an injection needle into the solution of calcium chloride. Smooth and spherical beads were formed under mechanical stirring. The wet beads obtained were suspended in glutaraldehyde solution at room temperature. Then, the beads were intensively washed with hot distilled water, air-dried, and stored at 4 °C.

The mechanism by which the beads deliver insulin into the small intestines and across the gastrointestinal mucosa depends on the pH sensitivity of alginate and chitosan. The alginate beads are stable in the acidic pH of the stomach. Once at the intestinal alkaline pH>6, they swell and start dissolving and releasing the Insulin. The chitosan component of the alginate beads has the effect of reinforcing their structure, increasing their stability in the intestinal alkaline pH. The beads swell by the absorption of water, which is kept in the network structure of polymer.

The swelling rate of the beads increased considerably to reach after 6 hours values of 550%, and then decreased slightly due to the decomplexation of the beads after 24 hours. The cumulative release of insulin in intestinal alkaline pH seems to be proportional to the swelling rate of the beads.

IM: What happens to the beads once they reach the gastrointestinal tract? And how safe are the polymers used to carry them?

Mr. Tahtat: As explained above, the beads swell in gastrointestinal tract pH and release the insulin continuously for six hours; beads with different proportion of alginate and chitosan result in varying release rates. In terms of the safety of the beads, as we mentioned earlier, since alginate and chitosan are polysaccharides, biodegradable, biocompatible and non-toxic, the beads are expected to be very safe. However, this remains to be confirmed with cytotoxicity studies.

IM: Would you be able to achieve a therapeutic dose of Insulin in the blood using this delivery method and have you done any in vitro studies to confirm that?

Mr. Tahtat: Yes it possible to achieve a therapeutic dose of insulin in the blood using this delivery method. In vitro studies showed that the cumulative insulin release in simulated intestinal fluid for the beads Alginate/Chitosan with different proportion reached between 90.5% and 70.2 % in 6 hours, the rate 100% was reached after 24 hours.

The conversion of cumulative release in IU allowed an appreciating of the quantity of insulin released in the intestinal media in 6 hours. The amounts of cumulative insulin release of beads with different proportion are between 16.11 IU and 30.29 IU. The quantity of insulin released (IU) in the intestinal medium (SIF) without the quantity released in the gastric medium (SGF) was adequate in comparison with the recommendations for the appropriate insulin dosage to meet the glycemic goals ranging between 10 to 20 IU per administration.

IM: What is the potential for this technology to be commercialised and available in the clinic, and are there any plans to take this into the industry?

Mr. Tahtat: The potential for this technology is immense. With the low cost formulation process and the simple steps involved, the procedure could be easily scaled up. The biomaterials used are readily available and very abundant in nature. However, more clinical studies are needed before the technology can reach the clinic, including toxicity and long terms safety studies. The drug development process is a very lengthy path, with many steps and risks at each step. In terms of our plans, we would need approval from the relevant health authorities before any plans to take this into the industry.

IM: Thank you again for speaking to Inspire Magazine and all the best with your future endeavours

Mr. Tahtat: Thank you very much for the opportunity to talk about this research and all my best wishes to you and inspire magazine.

About the Author

Romaissa Asme Boussahel author

Dr. Romaissa Asme Boussahel obtained her PhD from the School of Pharmacy, University of Nottingham, her work focuses on drug delivery, tissue engineering and regenerative medicine with a particular focus on growth factor delivery formulations and bone regeneration. She is Co-founder and Associate Editor of Inspire Magazine.

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Event Report | The 2014 Algerian Paper of the Year Awards | Inspire MagazinePosted on  2:53 pm - Feb 7, 2015

[…] Interview with the winners can be accessed here. […]

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